NCT03789591

Hydroxyurea Optimization Through Precision Study

Hydroxyurea Optimization Through Precision Study (HOPS): A Prospective, Multi-center, Randomized Trial of Personalized, Pharmacokinetics-guided Dosing of Hydroxyurea Versus Standard Weight-based Dosing for Children With Sickle Cell Anemia.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: Lifespan · Academic / Other
• Sex: All
• Age: 6 Months – 21 Years
• Healthy volunteers: Not accepted

Summary

Hydroxyurea Optimization through Precision Study (HOPS) is a prospective, multi-center, randomized trial that will directly compare a novel, individualized dosing strategy of hydroxyurea to standard weight-based dosing for children with SCA. The primary objective of the study is to evaluate whether a pharmacokinetics-based starting hydroxyurea dose thieves superior fetal hemoglobin response to to standard weight-based initial dosing. Patients will be recruited from the pediatric sickle cell clinic at Cincinnati Children's Hospital Medical Center and from additional pediatric sickle cell centers within the United States.

Detailed description

The trial will recruit patients who have decided to initiate hydroxyurea therapy. All participants will have pharmacokinetics studies performed at baseline, following a 20 mg/kg oral dose of hydroxyurea. Pharmacokinetic sampling will use a sparse sampling approach, requiring collection of blood at 3 time points (15 minutes, 60 minutes, 180 minutes) following the hydroxyurea dose. Enrolled participants will be randomized to receive either hydroxyurea using a starting dose of 20 mg/kg/day (Standard Arm) or a personalized PK-guided dose (Alternative Arm) to target an area under the curve (AUC) of 115 mg\*h/L based to approximate hydroxyurea exposure seen when patients are escalated to maximum tolerated dose (MTD). Following randomization and selection of the initial dose, participants in both arms will follow the same procedures of laboratory medication holds for hematological toxicity. The primary endpoint is fetal hemoglobin (HbF) six months following the initiation of hydroxyurea therapy with the hypothesis that participants starting with a PK-guided dose will achieve HbF at least 5% greater than those starting with a 20 mg/kg dose. Based upon the estimated number of new hydroxyurea starts at each site, it is anticipated that it will take 24 months to enroll the 116 participants required to achieve sufficient power to assess the primary endpoint. The study will conclude for each participant 12 months following hydroxyurea initiation.

Conditions

• Sickle Cell Disease
• Sickle Cell Anemia

Interventions

Type	Name	Description
DRUG	Hydroxyurea	The alternative arm will use PK data to choose a starting hydroxyurea dose to achieve an AUC of 115 mg\*h/L to approximate maximum tolerated dose. On the standard arm, participants will start at the traditional, weight-based dose of 20 mg/kg/day. Following selection of the starting dose, all participants will follow the same dose escalation and laboratory monitoring procedures.

Timeline

• Start date: 2019-01-17
• Primary completion: 2025-03-19
• Completion: 2025-03-19
• First posted: 2018-12-28
• Last updated: 2025-06-18

Locations

13 sites across 1 country: United States

Regulatory

• FDA-regulated drug study